PB2150: RELATIONSHIP BETWEEN P16 AND P53 CO-EXPRESSION AND SURVIVAL IN PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA
Authors: E. Vaneeva, A. Turubanova, M. Sarpova, D. Dyakonov, V. Rosin, S. Samarina
Journal: HemaSphere (2022)

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin’s lymphoma. The p16 protein is a representative of the family of inhibitors of cyclin-dependent kinases (INK4; Cdk). It is involved in the regulation of the cell cycle by destroying Cdk4/Cdk6 complexes with cyclins D, blocking the transition of the cell from G1 to S phase. The protein is encoded by the tumor suppressor gene CDKN2A (9p21), aberrations of which are detected in 15-30% of DLBCL cases. The p53 protein is a transcription factor. Its activation leads to cell cycle arrest, replication of damaged DNA, or cell apoptosis. Mutations in the TP53 gene encoding this protein occur in 20% of patients. It is known that high isolated expression of p16, p53 is associated with low overall (OS) and progression-free (PFS) survival of patients with DLBCL. However, there are no data on the significance of the combined expression of these proteins. Aims: Assesment of relationship between the co-expression p16 and p53 proteins and the survival of patients with DLBCL. Methods: Tumor tissue biopsies (paraffin blocks) obtained from 66 patients with newly diagnosed DLBCL (median age - 58 years) were used as material for the study. All patients received R-CHOP chemotherapy. The determination of the relative number of tumor cells expressing p16, p53 was carried out using immunohistochemical and morphometric methods. The threshold value of p16, p53 expression was calculated by enumeration method of data using a log-rank test when comparing survival curves with different threshold values. Quantitative values ​​of protein expression were converted into binary indicators. For p16, the threshold was 9% of positive tumor cells, for p53 - 35%. According to the established criteria, all subjects were divided into groups with high (+) [≥9% for p16; ≥35% for p53] and low (-) [<9% for p16; <35% for p53] protein expression. The five-year OS and PFS were calculated using the Kaplan-Meier method (log-rank test). The relationship of different variants of p16 and p53 co-expression with the course of DLBCL was analyzed. Results: The median 5-year survival of patients with DLBCL was 43 months. The highest 5-year OS (86%) was recorded in the group of patients with simultaneously low expression of markers (p16-/p53-; n=25). In subjects with high expression of one of the proteins (p16+/p53- and p16-/p53+; n=34), it was 21.6%. Patients with a simultaneous combination of high expression of markers (p16+/p53+; n=7) did not survive to the end of the observation period (0%). Using Cox regression analysis, it was found that in patients with p16+/p53+, the risk of developing an adverse event was 13.6 times higher than in the group of subjects with p16-/p53- (HR=13.6; 95% CI=10.2 -37.7). Intergroup differences in the analysis of PFS did not reach statistical significance (p=0.087). Summary/Conclusion: Сo-expression of p16+/p53+ biomarkers is associated with lower OS in DLBCL patients compared to other combinations of their expression.